Nitric oxide kinetics during hypoxia in proximal tubules: Effects of acidosis and glycine

Muhammad Yaqoob, Charles L. Edelstein, Eric Wieder, Ahmed M. Alkhunaizi, Patricia E. Gengaro, Raphael A. Nemenoff, Robert W. Schrier

Research output: Contribution to journalArticle

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Abstract

In the present study, we directly monitored nitric oxide (NO) with an amperometric NO-sensor in suspensions of rat proximal tubules. Hypoxia-stimulated NO generation was characterized by an initial rise and a subsequent sustained increase which preceded cell membrane damage as assessed by lactic dehydrogenase (LDH) release. In contrast, the NO concentration remained unmeasurable in normoxic controls. Nitro-L-arginine-methyl ester (L-NAME) prevented the hypoxia-induced increase in NO in a dose dependent manner in parallel with incremental cytoprotection. The hypoxia-induced elevation in NO and the associated membrane injury were both markedly prevented by extracellular acidosis (pH 6.95). In vitro proximal tubular nitric oxide synthase (NOS) activity (3H-arginine to 3H-citrulline assay) was pH-dependent with optimum activity at pH 8.0 and greatly reduced activity at acidic pH even in the presence of calcium and co-factors. However, glycine, a well recognized cytoprotective agent, did not attenuate the NO concentration during hypoxia. The present study therefore provides direct evidence that NO is generated by rat proximal tubules during hypoxia and demonstrates that the protective effect of low pH against hypoxic rat tubular injury is associated with an inhibition of this NO production.

Original languageEnglish (US)
Pages (from-to)1314-1319
Number of pages6
JournalKidney International
Volume49
Issue number5
StatePublished - 1996
Externally publishedYes

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Acidosis
Glycine
Nitric Oxide
Hypoxia
Citrulline
Cytoprotection
NG-Nitroarginine Methyl Ester
Wounds and Injuries
Nitric Oxide Synthase
Arginine
Suspensions
Oxidoreductases
Milk
Cell Membrane
Calcium
Membranes

ASJC Scopus subject areas

  • Nephrology

Cite this

Yaqoob, M., Edelstein, C. L., Wieder, E., Alkhunaizi, A. M., Gengaro, P. E., Nemenoff, R. A., & Schrier, R. W. (1996). Nitric oxide kinetics during hypoxia in proximal tubules: Effects of acidosis and glycine. Kidney International, 49(5), 1314-1319.

Nitric oxide kinetics during hypoxia in proximal tubules : Effects of acidosis and glycine. / Yaqoob, Muhammad; Edelstein, Charles L.; Wieder, Eric; Alkhunaizi, Ahmed M.; Gengaro, Patricia E.; Nemenoff, Raphael A.; Schrier, Robert W.

In: Kidney International, Vol. 49, No. 5, 1996, p. 1314-1319.

Research output: Contribution to journalArticle

Yaqoob, M, Edelstein, CL, Wieder, E, Alkhunaizi, AM, Gengaro, PE, Nemenoff, RA & Schrier, RW 1996, 'Nitric oxide kinetics during hypoxia in proximal tubules: Effects of acidosis and glycine', Kidney International, vol. 49, no. 5, pp. 1314-1319.
Yaqoob M, Edelstein CL, Wieder E, Alkhunaizi AM, Gengaro PE, Nemenoff RA et al. Nitric oxide kinetics during hypoxia in proximal tubules: Effects of acidosis and glycine. Kidney International. 1996;49(5):1314-1319.
Yaqoob, Muhammad ; Edelstein, Charles L. ; Wieder, Eric ; Alkhunaizi, Ahmed M. ; Gengaro, Patricia E. ; Nemenoff, Raphael A. ; Schrier, Robert W. / Nitric oxide kinetics during hypoxia in proximal tubules : Effects of acidosis and glycine. In: Kidney International. 1996 ; Vol. 49, No. 5. pp. 1314-1319.
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